行政院國家科學委員會專題研究計畫結案報告:腦部功能性磁性振造影之機制及臨床應用的研發（3/3）

The purpose of this two-year study is to investigate the correlation of magnetic resonance imaging (MRI) and histomorphological changes in a focal brain ischemia model of rat. In the first-year project, focal cerebral ischemia was produced with a predetermined duration. MR imaging is carried out with different pulse sequences of T1WI, T2WI, PDWI and DWI. Histomorphological study included histochemical stains with H/E, and GFAP. In the second year, we emphasized the effect of different post-stroke duration. The “early” changes of the brain images as well as histochemistry were studied. We also performed artificial neural net analsysis on the images obtained in these two years. The purpose was to improve the power of the imaging technique in differentiating severity and stage of stroke. The results showed in the acute stage of stroke, only T2WI and DWI are of great value in the detection of ischemic infarction. In histomorphological study, the H/E represented a more complete or laterstage change of ischemic infarction. GFAP revealed ischemic change of different severity and might indicate incomplete or earlier ischemic change. However, the quantitative study revealed that even the most sensitive DWI was not able to show up all area with partial and complete ischemic change as in the histochmical stain of GFAP. As for the earlier ischemic changes in histomorphology and MR image, the study revealed less satisfactory resutls. Neither H/E nor GFAP can reflect different severity of stroke. This is because neuroanl damage, reactive gliosis or loss of GFAP has not yet completed in such a short duration after an ischemic stroke. The performance of the MR images in such early change of stroke is also poor. Although artificial neural net did help with further analysis of MR images of stroke, it depends on the knowledge of the original images, histomorphology and histochemistry of the ischemic lesions.本研究利用兩年的時間，分階段研究動物模式的實驗性局部腦缺血的組織型態化學與各種磁振造影技術之間的關聯性。第一年，以定時間動脈結紮與重灌流的實驗來蒐集各種磁振造影脈衛序列( Tlwi , TZwi , PDwi , Dwi ）的訊號強度與動物的缺血性腦中風不同組織型態化學( H / E , 5100 , GFAP ）變化之定量關係。第二年則研究不同長短的中風復時間之腦組織缺血性變化與磁振影像之定量關係。並將兩年的結果以類神經網路的方法進行分析試圖改善影像對於不同中風時間及腦組織缺血嚴重度的鑑別能力。 結果顯示，在急性（24-72 小時）缺血性腦中風的情況下只有TZwi 與擴散造影技術，具偵測之價值。組織化學方面，H/E其所代表的意義是較慢性及完整之缺血變化，其變化面積較小。而GFAP 則可反應出不同嚴重度之缺血反應。其染色喪失，代表了完整嚴重之缺血性變化。染色增加之部分，代表了部分或較輕度之缺血 性變化。其可能代表腦缺血的半影區。對於組織型態化學中的GFAP 的發現，擴散影像技術並無法完全代表其範圍。至於更早期（2 -6 小時內）的缺血性變化及半影區的與組織型態學的變化則不論以H / E 或GFAP 染色觀察皆無法反應出不同嚴重度之缺血反應。因為在數小時內神經細胞死亡及膠質細胞增生之組織型態學以及GFAP 染色喪失或反應性增加之組織化學的變化皆尚未完成。磁振影像對於早期( 2 -6 小時內）缺血性腦中風的偵測功能並不完善，擴散造影（57 . 1 % , n = 14 ）與TZwi ( 2 1 . 4 % , n = 14 ）都只有偏低的早期顯現率。類神經網路的分析雖可將不同嚴重度之缺血區域分出。然而其個別區域所代表之臨床或病理之意義，端賴研究者進一步依據原有磁振影像，組織型態學以及組織化學之基礎知識予以進一步闡釋方具價值。The purpose of this two-year study is to investigate the correlation of magnetic resonance imaging (MRI) and histomorphological changes in a focal brain ischemia model of rat. In the first-year project, focal cerebral ischemia was produced with a predetermined duration. MR imaging is carried out with different pulse sequences of T1WI, T2WI, PDWI and DWI. Histomorphological study included histochemical stains with H/E, and GFAP. In the second year, we emphasized the effect of different post-stroke duration. The ¡§early¡¨ changes of the brain images as well as histochemistry were studied. We also performed artificial neural net analsysis on the images obtained in these two years. The purpose was to improve the power of the imaging technique in differentiating severity and stage of stroke. The results showed in the acute stage of stroke, only T2WI and DWI are of great value in the detection of ischemic infarction. In histomorphological study, the H/E represented a more complete or later- stage change of ischemic infarction. GFAP revealed ischemic change of different severity and might indicate incomplete or earlier ischemic change. However, the quantitative study revealed that even the most sensitive DWI was not able to show up all area with partial and complete ischemic change as in the histochmical stain of GFAP. As for the earlier ischemic changes in histomorpho logy and MR image, the study revealed less satisfactory resutls. Neither H/E nor GFAP can reflect different severity of stroke. This is because neuroanl damage, reactive gliosis or loss of GFAP has not yet completed in such a short duration after an ischemic stroke. The performance of the MR images in such early change of stroke is also poor. Although artificial neural net did help with further analysis of MR images of stroke, it depends on the knowledge of the original images, histomorphology and histochemistry of the ischemic lesions

行政院國家科學委員會專題研究計畫成果報告:腦部功能磁性振造之機制及臨床應用的研發(2/3)─實驗性局部缺血模式下之腦中風的組織型態學及磁共振影像之相關性(2/3)

本研究之目的在於透過實驗性局部腦 缺血的動物模式與組織型態化學及磁振 造影技術，來探討缺血性腦中風的可能機 制。驗證缺血性腦梗塞的理論腦缺血半 影區的假說。 第一年計劃，以定時間動脈結紮與重灌 流的實驗性局部腦缺血動物模式來蒐集 各類磁振造影脈衝序列(T1WI, T2WI, PDWI, DWI)下各種影像參數。以及研究 這些參數下的造影訊號強度與動物的缺 血性腦中風其不同組織型態化學(H/E, S100, GFAP)所得的各種腦組織缺血性變 化之定量相關性。 結果顯示，在本研究觀察之急性缺血性 腦中風的情況下只有T2WI 與擴散造影技 術，具偵測之價值。組織化學的分析方 面，H/E 染色觀察的是神經死亡及膠質細 胞之增生所代表的是較慢性及完整之缺 血變化，如預期的其產生變化之面積較 小。而GFAP 則可反應出不同嚴重度之缺 血反應。其染色之喪失，代表了完整嚴重 之缺血性變化。染色程度增加之部分，代 表了部分或較輕度之缺血性變化。此一區 域可能代表了腦缺血半影區。然而相對於 組織型態化學中的GFAP 的發現，即使以 對急性缺血性腦梗塞較敏感之擴散影像 技術也無法完全代表其範圍 。至於更早期的缺血性變化及半影區的 磁振影像與組織型態學的變化則是目前 尚在進行之計劃所將解答的。本研究之目的在於透過實驗性局部腦 缺血的動物模式與組織型態化學及磁振 造影技術，來探討缺血性腦中風的可能機 制。驗證缺血性腦梗塞的理論腦缺血半 影區的假說。 第一年計劃，以定時間動脈結紮與重灌 流的實驗性局部腦缺血動物模式來蒐集 各類磁振造影脈衝序列(T1WI, T2WI, PDWI, DWI)下各種影像參數。以及研究 這些參數下的造影訊號強度與動物的缺 血性腦中風其不同組織型態化學(H/E, S100, GFAP)所得的各種腦組織缺血性變 化之定量相關性。 結果顯示，在本研究觀察之急性缺血性 腦中風的情況下只有T2WI 與擴散造影技 術，具偵測之價值。組織化學的分析方 面，H/E 染色觀察的是神經死亡及膠質細 胞之增生所代表的是較慢性及完整之缺 血變化，如預期的其產生變化之面積較 小。而GFAP 則可反應出不同嚴重度之缺 血反應。其染色之喪失，代表了完整嚴重 之缺血性變化。染色程度增加之部分，代 表了部分或較輕度之缺血性變化。此一區 域可能代表了腦缺血半影區。然而相對於 組織型態化學中的GFAP 的發現，即使以 對急性缺血性腦梗塞較敏感之擴散影像 技術也無法完全代表其範圍 。至於更早期的缺血性變化及半影區的 磁振影像與組織型態學的變化則是目前 尚在進行之計劃所將解答的

行政院國家科學委員會專題研究計畫成果報告:記憶系統中之自動與控制過程 -- 以電腦化的神經心理檢查與事件相關電位為研究方法

傳統上將認知功能時的覺知程度二分成自動化或控制性模式。熟悉的常規性工作，交給 自動化模式去處理。複雜的工作則會啟動控制性模式，比如在處理上超出日常常規性工 作之複雜度者，其次舊資料需用新方式加以處理時，或者必須加以創新處理的新資訊。 控制性模式的量測，以處理”隨機非結構”表徵之資訊時的反應加以量測。自動化模式的 量測則針對俱”結構性序列”表徵之訊息的處理反應加以量測。事件相關電位則以32 頻道 之NeuroScan 腦波機予以記錄。自動與控制則以240 毫秒正波時之平均值以雙楔內插法 運算得之，並計算其組間T 值腦電波圖譜。刺激用之幾何圖形呈現在15 吋之液晶銀幕上 並以60 公分之距離來觀看。每圖呈現一秒並有300 毫秒之空白間格。對於第一組(8 個 圖形)呈現之圖形，受試者須全神貫注並加以牢記。接著受試者須在第一及第二組(另8 個圖形)隨機交錯出現之圖形進行辨認及”是”、”否”出現過之回答。第三階段辨認測試時 又加入16 個從未出現過之圖形，此時並同時記錄事件相關電位腦波，每組圖形會有總共 64 腦波之記錄。 實驗結果顯示，處理俱”結構性序列”表徵之訊息的反應時間(平均時長: 17.1 ± 3.1 秒)較 處理”隨機非結構”表徵之資訊時的反應時間(平均時長: 15.5 ± 3.5 秒)為長。兩者之相差 顯著(P=0.0002)。反應正確率也以處理”隨機非結構”表徵之資訊時為高(”隨機非結構” : 6.6 ± 4.3; ”結構性序列” : 7.4±3.8)，兩者相差亦顯著(P=0.00569)。 事件相關電位腦波圖譜的研究，支持較熟悉之自動化制性模式其大腦部位在較後 區，而不熟悉之新訊息的控制性模式則需動員大腦前區之資源加以應對處理。總之，本 研究計畫運用電腦化的神經心理檢查與事件相關電位的研究方法探討了記憶系統中之自 動與控制的過程並見證了其表現與其在大腦內的活性變化。The conventional concept about the level of awareness during cognitive processing can be divided in a dichotomy way into automatic and controlled processes. Routine tasks that we are rather familiar with go through automatic process. Complex tasks invoke controlled process when the level of complexity of a task requires more than routine processing, when old information must be considered in new ways or when the information is to be processed de novo. The measurement of the controlled process of the memory system was performed by using tasks with “random-disorganized” features, which invoked more awareness in handling the more complex situation. The measurement of the automatic process of the memory system was performed by using tasks with “structured-organized” features, which utilized less awareness in handling the less complex situation. ERP were recorded with a 32- channel ERP machine. Brain mappings were prepared at the mean latencies of P240 with the grand average of ERP using double spline interpolation. Between-group t-Maps were also constructed. Geometry shapes were presented to the subjects in a 15-inches LCD screen at about 60-cm distance. The shapes of the first group were presented for one second with an inter-break of about 300 ms. Subjects were instructed to pay full attention and to memorize them by heart. After the presentation the subjects were asked to recognize and to do a yes-no response on the shapes of the first group from a randomized presentation of shapes from the first (8 forms) and the 2nd group (8 forms). ERP were recorded during the 3rd stage of presentation and recognition test. Another 16 novel shapes that have never been presented joined in a random presentation sequence with the 1st and 2nd groups. In total 64 trials ERP were collected from each group for further analysis. It took longer to complete the “structured-organized” task (mean duration: 17.1 ± 3.1 sec) than to complete the “randomized-disorganized” task (mean duration: 15.5 ± 3.5 sec) with a statistic significant difference (p = 0.00002). The mean scores (correct – omission – commission) were lower (p = 0.00569) with “structured-organized” task (6.6 ± 4.3) than with “randomized- disorganized” task (7.4±3.8). In ERP study, the three conditions had similar waveforms especially the early components while their brain topographic mappings varied in the spatial distribution. The well-memorized targets induced activities over the bilateral parietal cortexes more on the right side. Those implicitly learned targets or de novo targets induced some frontal activities appeared in addition to parietal activities. In conclusion, “controlled process” recruits more brain resources but performs better in terms of speed and correct rates. ERP showed results compatible with that brain regions involved in this kind of automatic process are more posterior in location while the controlled process involves brain areas mostly within the frontal lobe